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1.
Bioorg Chem ; 104: 104246, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32911197

RESUMEN

Cryptotanshinone (1), a major bioactive constituent in the traditional Chinese medicinal herb Dan-Shen Salvia miltiorrhiza Bunge, has been reported to possess remarkable pharmacological activities. To improve its bioactivities and physicochemical properties, in the present study, cryptotanshinone (1) was biotransformed with the fungus Cunninghamella elegans AS3.2028. Three oxygenated products (2-4) at C-3 of cryptotanshinone (1) were obtained, among them 2 was a new compound. Their structures were elucidated by comprehensive spectroscopic analysis including HRESIMS, NMR and ECD data. All of the biotransformation products (2-4) were found to inhibit significantly lipopolysaccharide-induced nitric oxide production in BV2 microglia cells with the IC50 values of 0.16-1.16 µM, approximately 2-20 folds stronger than the substrate (1). These biotransformation products also displayed remarkably improved inhibitory effects on the production of inflammatory cytokines (IL-1ß, IL-6, TNF-α, COX-2 and iNOS) in BV-2 cells via targeting TLR4 compared to substrate (1). The underlying mechanism of 2 was elucidated by comparative transcriptome analysis, which suggested that it reduced neuroinflammatory mainly through mitogen-activated protein kinase (MAPK) signaling pathway. Western blotting results revealed that 2 downregulated LPS-induced phosphorylation of JNK, ERK, and p38 in MAPK signaling pathway. These findings provide a basal material for the discovery of candidates in treating Alzheimer's disease.


Asunto(s)
Antiinflamatorios no Esteroideos/farmacología , Inhibidores de la Colinesterasa/farmacología , Cunninghamella/metabolismo , Proteínas Quinasas Activadas por Mitógenos/antagonistas & inhibidores , Fenantrenos/farmacología , Receptor Toll-Like 4/antagonistas & inhibidores , Acetilcolinesterasa/metabolismo , Animales , Antiinflamatorios no Esteroideos/química , Antiinflamatorios no Esteroideos/metabolismo , Biotransformación , Línea Celular , Supervivencia Celular/efectos de los fármacos , Inhibidores de la Colinesterasa/química , Inhibidores de la Colinesterasa/metabolismo , Cunninghamella/química , Relación Dosis-Respuesta a Droga , Electrophorus , Ratones , Proteínas Quinasas Activadas por Mitógenos/metabolismo , Estructura Molecular , Oxígeno/metabolismo , Fenantrenos/química , Fenantrenos/metabolismo , Transducción de Señal/efectos de los fármacos , Relación Estructura-Actividad , Receptor Toll-Like 4/metabolismo
2.
Mar Drugs ; 18(3)2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32110865

RESUMEN

Aspergillus terreus has been reported to produce many secondary metabolites that exhibit potential bioactivities, such as antibiotic, hypoglycemic, and lipid-lowering activities. In the present study, two new thiodiketopiperazines, emestrins L (1) and M (2), together with five known analogues (3-7), and five known dihydroisocoumarins (8-12), were obtained from the marine-derived fungus Aspergillus terreus RA2905. The structures of the new compounds were elucidated by analysis of the comprehensive spectroscopic data, including high-resolution electrospray ionization mass spectrometry (HRESIMS), one-dimensional (1D) and two-dimensional (2D) nuclear magnetic resonance (NMR), and electronic circular dichroism (ECD) data. This is the first time that the spectroscopic data of compounds 3, 8, and 9 have been reported. Compound 3 displayed antibacterial activity against Pseudomonas aeruginosa (minimum inhibitory concentration (MIC) = 32 µg/mL) and antifungal activity against Candida albicans (MIC = 32 µg/mL). In addition, compound 3 exhibited an inhibitory effect on protein tyrosine phosphatase 1 B (PTP1B), an important hypoglycemic target, with an inhibitory concentration (IC)50 value of 12.25 µM.


Asunto(s)
Antibacterianos/farmacología , Aspergillus/química , Animales , Candida albicans/efectos de los fármacos , Cumarinas/química , Pruebas de Sensibilidad Microbiana , Océanos y Mares , Piperazinas/química , Pseudomonas aeruginosa/efectos de los fármacos
3.
Am J Physiol Endocrinol Metab ; 316(1): E73-E85, 2019 01 01.
Artículo en Inglés | MEDLINE | ID: mdl-30422704

RESUMEN

Increased circulating branched-chain amino acids (BCAAs) have been involved in the pathogenesis of obesity and insulin resistance (IR). However, evidence relating berberine (BBR), gut microbiota, BCAAs, and IR is limited. Here, we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet (HFD)-fed mice. BBR reorganized gut microbiota populations under both the normal chow diet (NCD) and HFD. Particularly, BBR noticeably decreased the relative abundance of BCAA-producing bacteria, including order Clostridiales; families Streptococcaceae, Clostridiaceae, and Prevotellaceae; and genera Streptococcus and Prevotella. Compared with the HFD group, predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment. Accordingly, the elevated serum BCAAs of HFD group were significantly decreased by BBR. Furthermore, the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by activation of the multienzyme branched-chain α-ketoacid dehydrogenase complex (BCKDC), whereas by inhibition of the phosphorylation state of BCKDHA (E1α subunit) and branched-chain α-ketoacid dehydrogenase kinase (BCKDK). The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes. Finally, data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs. Together, our findings clarified BBR improving IR associated not only with gut microbiota alteration in BCAA biosynthesis but also with BCAA catabolism in liver and adipose tissues.


Asunto(s)
Tejido Adiposo Blanco/efectos de los fármacos , Aminoácidos de Cadena Ramificada/efectos de los fármacos , Berberina/farmacología , Disbiosis/metabolismo , Microbioma Gastrointestinal/efectos de los fármacos , Resistencia a la Insulina , Hígado/efectos de los fármacos , Obesidad/metabolismo , 3-Metil-2-Oxobutanoato Deshidrogenasa (Lipoamida)/metabolismo , Células 3T3-L1 , Adipocitos/efectos de los fármacos , Adipocitos/metabolismo , Tejido Adiposo Blanco/metabolismo , Adulto , Aminoácidos de Cadena Ramificada/metabolismo , Animales , Diabetes Mellitus/metabolismo , Dieta Alta en Grasa , Hígado Graso , Femenino , Microbioma Gastrointestinal/genética , Intolerancia a la Glucosa , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Humanos , Hígado/metabolismo , Masculino , Metagenómica , Ratones , Persona de Mediana Edad , Proteínas Quinasas
4.
Molecules ; 23(6)2018 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-29874868

RESUMEN

Phyllodiumpulchellum has been traditionally used as a medicinal herb because of its health-promoting effects, such as its hepatoprotective and antioxidant activities. In the present study, the petroleum ether fraction, ethyl acetate fraction, n-butanol fraction, and aqueous fraction were successively obtained from the ethanol extract of P. pulchellum. Two fractions, ethyl acetate fraction and n-butanol fraction, were found to display hepatoprotective and antioxidant activities. Further chemical investigation of the active fractions led to the isolation of its main constituents, including 11 flavonoids (1⁻11) and 8 indole alkaloids (12⁻19). There were 9 flavonoids (1⁻9) that were obtained from the ethyl acetate fraction, and 2 flavonoids (10 and 11) and 8 alkaloids (12⁻19) from the n-butanol fraction. Compounds 1⁻11 and 16⁻19 were isolated for the first time from P. pulchellum, and 1, 2, 8, 11, and 18 were obtained from the genus Phyllodium initially. Subsequently, the isolated compounds were evaluated for their in vitro hepatoprotective effects on the human normal hepatocyte cell line L-O2 injured by d-galactosamine and radical scavenging activities against 1,1-diphenyl-2-picrylhydrazyl (DPPH). The flavonoids (-)-epigallocatechin (5) and (-)-epicatechin (6) exhibited prominent hepatoprotective activities with higher cell viability values (65.53% and 62.40% at 10 µM·mL-1, respectively) than the positive control, silymarin (61.85% at 10 µM·mL-1). In addition, compared with the positive control of vitamin C (IC50: 5.14 µg·mL-1), (-)-gallocatechin (3) and (-)-epigallocatechin (5) exhibited stronger antioxidant activities with IC50 values of 3.80 and 3.97 µg·mL-1, respectively. Furthermore, the total flavonoids from P. pulchellum were characterized using a high-performance liquid chromatography-linear ion trap quadrupole-Orbitrap-mass spectrometry (HPLC-LTQ-Orbitrap-MS). In total, 34 flavonoids were tentatively identified, which had not been previously reported from P. pulchellum. In addition, we performed a semi-quantitative analysis of the isolated flavonoids. The contents of compounds 1⁻11 were 3.88, 17.73, 140.35, 41.93, 27.80, 4.34, 0.01, 0.20, 9.67, 795.85, and 5.23 µg·g-1, respectively. In conclusion, this study revealed that the flavonoids that were isolated from P. pulchellum showed hepatoprotective and antioxidant activities, indicating that, besides alkaloids, the flavonoids should be the potential pharmacodynamic ingredients that are responsible for the hepatoprotective and antioxidant activities of P. pulchellum.


Asunto(s)
Antioxidantes/farmacología , Fabaceae/química , Hígado/efectos de los fármacos , Antioxidantes/química , Línea Celular , Cromatografía Líquida de Alta Presión/métodos , Hepatocitos/efectos de los fármacos , Humanos , Espectrometría de Masas/métodos , Relación Estructura-Actividad
5.
J Org Chem ; 82(9): 4774-4783, 2017 05 05.
Artículo en Inglés | MEDLINE | ID: mdl-28421761

RESUMEN

The asymmetric organocatalyzed diversity-oriented one-pot synthesis has been developed to construct chroman-2-one derivatives and other heterocyclic compounds with excellent efficiency and stereoselectivity. The reactions represent a challenging issue, since it altered the inherent selectivity profiles exhibited by the substrates of 2-hydroxycinnamaldehyde 1 and trans-ß-nitrostyrene 2, which was previously reported as the asymmetric oxa-Michael-Michael cascade to generate chiral chromans. It should be noted that polycyclic O,O-acetal-containing compounds, which are found in numerous natural products and biologically interesting molecules, could also be achieved in good yields with excellent enantioselectivity as a single diastereoisomer with five continuous stereogenic centers.

6.
Mar Drugs ; 15(7)2017 Jul 09.
Artículo en Inglés | MEDLINE | ID: mdl-28698495

RESUMEN

Currently, DNA topoisomerase I (Topo I) inhibitors constitute a family of antitumor agents with demonstrated clinical effects on human malignancies. However, the clinical uses of these agents have been greatly limited due to their severe toxic effects. Therefore, it is urgent to find and develop novel low toxic Topo I inhibitors. In recent years, during our ongoing research on natural antitumor products, a collection of low cytotoxic or non-cytotoxic compounds with various structures were identified from marine invertebrates, plants, and their symbiotic microorganisms. In the present study, new Topo I inhibitors were discovered from low cytotoxic and non-cytotoxic natural products by virtual screening with docking simulations in combination with bioassay test. In total, eight potent Topo I inhibitors were found from 138 low cytotoxic or non-cytotoxic compounds from coral-derived fungi and plants. All of these Topo I inhibitors demonstrated activities against Topo I-mediated relaxation of supercoiled DNA at the concentrations of 5-100 µM. Notably, the flavonoids showed higher Topo I inhibitory activities than other compounds. These newly discovered Topo I inhibitors exhibited structurally diverse and could be considered as a good starting point for the development of new antitumor lead compounds.


Asunto(s)
Productos Biológicos/química , Productos Biológicos/farmacología , ADN-Topoisomerasas de Tipo I/metabolismo , Inhibidores de Topoisomerasa I/química , Inhibidores de Topoisomerasa I/farmacología , Animales , Antozoos/química , Antineoplásicos/química , Antineoplásicos/farmacología , Hongos/química , Humanos , Plantas/química , Relación Estructura-Actividad
7.
Zhongguo Zhong Yao Za Zhi ; 40(21): 4223-8, 2015 Nov.
Artículo en Zh | MEDLINE | ID: mdl-27071261

RESUMEN

A comparable study were carried out by determination of trace elements on five marine-derived shell traditional Chinese medicine (TCM) (Ostreae Concha, Haliotidis Concha, Margaritifera Concha, Meretricis Concha, and Arcae Concha), which were recorded in the Chinese Pharmacopoeia (2010 version). Seven trace elements in 51 batches of this type of shell TCM were analyzed by Inductively Coupled Plasma Mass Spectrometry (ICP-MS), combined with principal component analysis (PCA) methods. The content of element Se, which exhibited significant differences among different drugs, could be used as a key element to distinguish this type of drugs. Meanwhile, the contents of elements Co, Cu, Mo, and Ba in Haliotidis Concha, Co and As in Margaritifera Concha, Mo and As in Meretricis Concha, Mo, As, and Ba in Arcae Concha, and Zn in Meretricis Concha were relatively stable. In the PCA plot, Arcae Concha and Meretricis Concha could be efficiently distinguished from Ostreae Concha together with Haliotidis Concha, and Margaritifera Concha. The results also showed a correlation with their medicinal function. In conclusion, trace elements in marine-derived shell TCM could not be neglected for their quality control.


Asunto(s)
Exoesqueleto/química , Organismos Acuáticos/química , Bivalvos/química , Oligoelementos/análisis , Animales , Espectrometría de Masas , Medicina Tradicional China
8.
Mar Drugs ; 12(4): 2019-35, 2014 Apr 03.
Artículo en Inglés | MEDLINE | ID: mdl-24705500

RESUMEN

Recently, the studies on the prevention and treatment of human papillomavirus (HPV) which is closely related to the cervical cancer and other genital diseases are attracting more and more attention all over the world. Marine-derived polysaccharides and other bioactive compounds have been shown to possess a variety of anti-HPV and related cancer activities. This paper will review the recent progress in research on the potential anti-HPV and related cancer agents from marine resources. In particular, it will provide an update on the anti-HPV actions of heparinoid polysaccharides and bioactive compounds present in marine organisms, as well as the therapeutic vaccines relating to marine organisms. In addition, the possible mechanisms of anti-HPV actions of marine bioactive compounds and their potential for therapeutic application will also be summarized in detail.


Asunto(s)
Antineoplásicos/farmacología , Antivirales/farmacología , Productos Biológicos/farmacología , Animales , Antineoplásicos/química , Antineoplásicos/aislamiento & purificación , Antivirales/química , Antivirales/aislamiento & purificación , Organismos Acuáticos/metabolismo , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Humanos , Infecciones por Papillomavirus/tratamiento farmacológico , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Polisacáridos/farmacología , Vacunas/administración & dosificación , Vacunas/aislamiento & purificación
9.
Zhongguo Zhong Yao Za Zhi ; 39(17): 3291-4, 2014 Sep.
Artículo en Zh | MEDLINE | ID: mdl-25522614

RESUMEN

The identification of five marine-derived shell traditional Chinese medicine (TCM) recorded in the Chinese Pharmacopoeia were studied. Using near infrared technology (NIR) combined with principal component analysis (PCA) methods, Ostreae Concha, Haliotidis Concha, and Margaritifera Concha could be efficiently distinguished from Meretricis Concha together with Arcae Concha. In the first principal components, Ostreae Concha exhibited obvious differences with high loadings in 4 236, 5 263, 7 142 cm(-1) concerning to the contents of CaCO3 and H2O in the samples. Arcae Concha and Meretricis Concha displayed significant differences with others in the second principal components, which can be illustrated by high loadings in 5 000 -4 430 cm(-1) areas. It is indicated that the second principal components might be related to organics which contained NH and CH groups, for example proteins. Meanwhile, our data showed a correlation between the function of these shell TCM and their distribution in the PCA plot. These results suggested that organic components in marine-derived shell TCM could not be neglected for their quality control.


Asunto(s)
Exoesqueleto/química , Medicina Tradicional China/métodos , Moluscos/química , Espectroscopía Infrarroja Corta/métodos , Animales , Carbonato de Calcio/análisis , Moluscos/clasificación , Análisis de Componente Principal , Agua de Mar , Especificidad de la Especie
10.
Mar Drugs ; 11(4): 1113-25, 2013 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-23549283

RESUMEN

This study was aimed at developing a sensitive and selective HPLC method with postcolumn fluorescence derivatization for the detection of propylene glycol alginate sodium sulfate (PSS) in rat plasma. Plasma samples were prepared by a simple and fast ultrafiltration method. PSS was extracted from rat plasma with D-glucuronic acid as internal standard. Isocratic chromatographic separation was performed on a TSKgel G2500 PWxL column with the mobile phase of 0.1 M sodium sulfate at a flow rate of 0.5 mL/min. Analyte detection was achieved by fluorescence detection (FLD) at 250 nm (excitation) and 435 nm (emission) using guanidine hydrochloride as postcolumn derivatizing reagent in an alkaline medium at 120 °C. The calibration curve was linear over a concentration range of 1-500 µg/mL, and the lower limit of detection (LLOD) was found to be 250 ng/mL. This validated method was applied successfully to the pharmacokinetic study of PSS and PSS-loaded poly lactic-co-glycolic acid (PLGA) nanoparticles (PSS-NP) in rat plasma after a single intravenous (PSS only) and oral administration (PSS and PSS-NP). Significant differences in the main pharmacokinetic parameters of PSS and PSS-NP were observed. The relative bioavailability of PSS-NP was 190.10% compared with PSS which shows that PSS-NP can improve oral bioavailability.


Asunto(s)
Alginatos/farmacocinética , Cromatografía Líquida de Alta Presión/métodos , Ácido Láctico/química , Nanopartículas , Ácido Poliglicólico/química , Administración Oral , Alginatos/análisis , Alginatos/química , Animales , Disponibilidad Biológica , Calibración , Femenino , Fluorescencia , Inyecciones Intravenosas , Límite de Detección , Masculino , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas , Ratas Wistar , Sulfatos/química
11.
Mar Drugs ; 10(12): 2795-816, 2012 Dec 12.
Artículo en Inglés | MEDLINE | ID: mdl-23235364

RESUMEN

Recently, the studies on the antiviral activities of marine natural products, especially marine polysaccharides, are attracting more and more attention all over the world. Marine-derived polysaccharides and their lower molecular weight oligosaccharide derivatives have been shown to possess a variety of antiviral activities. This paper will review the recent progress in research on the antiviral activities and the mechanisms of these polysaccharides obtained from marine organisms. In particular, it will provide an update on the antiviral actions of the sulfated polysaccharides derived from marine algae including carrageenans, alginates, and fucans, relating to their structure features and the structure-activity relationships. In addition, the recent findings on the different mechanisms of antiviral actions of marine polysaccharides and their potential for therapeutic application will also be summarized in detail.


Asunto(s)
Antivirales/farmacología , Productos Biológicos/farmacología , Polisacáridos/farmacología , Alginatos/química , Alginatos/aislamiento & purificación , Alginatos/farmacología , Animales , Antivirales/química , Antivirales/aislamiento & purificación , Organismos Acuáticos/química , Productos Biológicos/química , Productos Biológicos/aislamiento & purificación , Carragenina/química , Carragenina/aislamiento & purificación , Carragenina/farmacología , Humanos , Polisacáridos/química , Polisacáridos/aislamiento & purificación , Relación Estructura-Actividad
12.
Mar Drugs ; 10(5): 1180-1191, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22822365

RESUMEN

To compare the chemical differences between the medicinal and cultured oyster shells, their chemical profiles were investigated. Using the ultra performance liquid chromatography-electron spraying ionization-mass spectrometry (UPLC-ESI-MS), combined with principal component analysis (PCA) and orthogonal projection to latent structures discriminant analysis (OPLS-DA), the discrimination of the chemical characteristics among the medicinal and cultured oyster shells was established. Moreover, the chemometric analysis revealed some potential key compounds. After a large-scale extraction and isolation, one target key compound was unambiguously identified as caffeine based on extensive spectroscopic data analysis (1D and 2D NMR, MS, and UV) and comparison with literature data.


Asunto(s)
Cafeína/química , Cafeína/aislamiento & purificación , Ostreidae/química , Animales , Cromatografía Líquida de Alta Presión/métodos , Análisis Discriminante , Medicina Tradicional China , Análisis de Componente Principal/métodos , Espectrometría de Masa por Ionización de Electrospray/métodos
13.
Acta Pharmacol Sin ; 31(11): 1500-7, 2010 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-20953211

RESUMEN

AIM: To investigate the population pharmacokinetics of recombinant human tumor necrosis factor receptor-Fc fusion protein (rhTNFR-Fc) administered via subcutaneous (SC) injection in healthy Chinese volunteers and in Chinese patients with ankylosing spondylitis (AS). METHODS: Thirty-two healthy volunteers were randomly assigned to receive a single SC injection of 12.5, 25, 37.5, or 50 mg of rhTNFR-Fc. Twenty male patients with moderate AS were randomly assigned to receive seven consecutive SC injections of rhTNFR-Fc at either 25 mg twice a week (BIW) or 50 mg once a week (QW). Population pharmacokinetic (PK) analysis was applied to obtain PK parameters of rhTNFR-Fc by the NONMEM method. RESULTS: The data were best described by a one-compartment model with lag time. We found that gender had a significant effect on the apparent clearance (CL/F), with the male CL/F ratio being only 0.665 times the female ratio; the absorption coefficient (F) of multiple dosages of rhTNFR-Fc was only 0.674 times that of a single dosage. The outcome parameters were CL/F (female: 0.168 L/h, male: 0.110 L/h), the apparent volume of distribution (Vd/F: 15.5 L), the absorption rate constant (Ka) (single dosage: 0.0605 h⁻¹, multiple dosage: 0.0408 h⁻¹), and the lag time (T(lag): 1.03 h). The inter-individual variability in the CL/F, Vd/F, Ka, and T(lag) were 33.3%, 42.7%, 55.6%, and 81.8%, respectively. CONCLUSION: Chinese females have a higher CL/F than Chinese males, and multiple dosings can significantly decrease the absorption of rhTNFR-Fc (SC). The population PK parameters of rhTNFR-Fc in healthy Chinese volunteers and patients with AS were similar to those reported for subjects in published American studies.


Asunto(s)
Antirreumáticos/farmacocinética , Inmunoglobulina G/sangre , Receptores del Factor de Necrosis Tumoral/sangre , Proteínas Recombinantes de Fusión/farmacocinética , Caracteres Sexuales , Espondilitis Anquilosante/metabolismo , Absorción , Adulto , Antirreumáticos/sangre , China , Relación Dosis-Respuesta a Droga , Etanercept , Femenino , Humanos , Inyecciones Subcutáneas , Masculino , Proteínas Recombinantes de Fusión/sangre , Espondilitis Anquilosante/sangre , Distribución Tisular , Adulto Joven
14.
BMC Complement Med Ther ; 20(1): 243, 2020 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-32758223

RESUMEN

BACKGROUND: Lung cancer has the highest morbidity and mortality in the world and novel treatment strategies are still needed. Haimufang decoction (HMF) is a patented clinical prescription of traditional Chinese medicine for lung cancer treatment. HMF is composed of four herbs and has been applied clinically in advanced cancer patients. However, its therapeutic mechanisms are still unclear. This study aims to elucidate the possible mechanisms of HMF for the treatment of lung cancer. METHODS: 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide assay was applied for evaluating the proliferative effect of HMF in lung cancer cells and monocyte macrophage RAW264.7 cells. Flow cytometer was used to detect the effects of HMF on cell cycle and apoptosis, and western blotting was employed to explore the potential apoptotic mechanisms of HMF on lung cancer cells. For immunomodulatory effect, co-culture system was used to detect the activation of macrophage RAW264.7 cells when treated with HMF, and neutral red assay was used to measure the effect of HMF on the phagocytosis of the activated macrophages. Enzyme linked immunosorbent assay, flow cytometer, and immunofluorescence staining method were employed for the investigation on the underlying mechanisms of the immunomodulatory effect on RAW264.7 induced by HMF. RESULTS: HMF inhibited the proliferation, induced S phase cell cycle arrest, and stimulated apoptosis in lung cancer NCI-H1975 cells, while had negligible cytotoxicity on macrophage RAW264.7 cells. Moreover, HMF could activate macrophage RAW264.7 cells and promote the inhibition activity of RAW264.7 cells against lung cancer cells. And also, HMF activated macrophages and increased their phagocytic activity in a concentration-dependent manner. HMF increased the expression of macrophage activation marker CD40, the level of nitric oxide, the generation of intracellular reactive oxygen species, as well as M1 macrophages cytokines including tumor necrosis factor-α, interleukin-1ß, interleukin 12 p70, and interleukin 6. Further investigation showed that HMF induced M1 but not M2 phenotype polarization in RAW264.7 cells. CONCLUSIONS: HMF can mainly exert anticancer activity via (1) cytotoxicity to human lung cancer cells by proliferation inhibition, cell cycle arrest, and apoptosis induction; and also via (2) immunomodulation via macrophage cells activation and M1 phenotype polarization induction.


Asunto(s)
Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Puntos de Control del Ciclo Celular/efectos de los fármacos , Medicamentos Herbarios Chinos/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Macrófagos/efectos de los fármacos , Animales , Línea Celular Tumoral , Humanos , Ratones , Células RAW 264.7
15.
Acta Pharmacol Sin ; 30(7): 973-9, 2009 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-19543300

RESUMEN

AIM: The pro-fibrogenic cytokine transforming growth factor-beta 1 (TGF-beta1) has attracted much attention for its potential role in the etiology of idiopathic pulmonary fibrosis (IPF). Here, we demonstrate that MS80, a novel sulfated oligosaccharide extracted from seaweed, can bind TGF-beta1. The aim of the present study was to determine whether MS80 is capable of combating TGF-beta1-mediated pulmonary fibrotic events both in vitro and in vivo, and to investigate the possible underlying mechanisms. METHODS: Surface plasmon resonance was used to uncover the binding profiles between the compound and TGF-beta. MTT assay, flow cytometry, Western blot analysis, BCA protein assay and SDS-PAGE gelatin zymography were used to probe the antifibrotic mechanisms of MS80. The in vivo fibrotic efficacy was evaluated in a bleomycin instillation-induced rat model. RESULTS: We report that MS80, a new kind of sulfated oligosaccharide extracted from seaweed, inhibits TGF-beta1-induced pulmonary fibrosis in vitro and bleomycin-induced pulmonary fibrosis in vivo. Our results indicated that MS80 competitively inhibited heparin/HS-TGF-beta1 interaction through its high binding affinity for TGF-beta1. Moreover, MS80 arrested TGF-beta1-induced human embryo pulmonary fibroblast (HEPF) cell proliferation, collagen deposition and matrix metalloproteinase (MMP) activity. Intriguingly, MS80 deactivated both the ERK and p38 signaling pathways. MS80 was also a potent suppressor of bleomycin-induced rat pulmonary fibrosis in vivo, as evidenced by improved pathological settings and decreased lung collagen contents. CONCLUSION: MS80 in particular, and perhaps oligosaccharide in general, offer better pharmacological profiles with appreciably few side effects and represent a promising class of drug candidates for IPF therapy.Acta Pharmacologica Sinica (2009) 30: 973-979; doi: 10.1038/aps.2009.86; published online 22 June 2009.


Asunto(s)
Oligosacáridos/uso terapéutico , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/prevención & control , Factor de Crecimiento Transformador beta1/metabolismo , Animales , Bleomicina/efectos adversos , Líquido del Lavado Bronquioalveolar/química , Ciclo Celular/fisiología , Proliferación Celular , Quinasas MAP Reguladas por Señal Extracelular/metabolismo , Humanos , Metaloproteinasas de la Matriz/metabolismo , Estructura Molecular , Oligosacáridos/química , Unión Proteica , Fibrosis Pulmonar/inducido químicamente , Fibrosis Pulmonar/patología , Ratas , Ratas Wistar , Algas Marinas/química , Transducción de Señal/fisiología , Proteínas Quinasas p38 Activadas por Mitógenos/metabolismo
16.
J Asian Nat Prod Res ; 11(10): 851-5, 2009 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-20183245

RESUMEN

Two new metabolites, sarcophytonone (1) and sarcophytonamine (2), have been isolated from the Hainan soft coral Sarcophyton crassocaule. Their structures were elucidated on the basis of a detailed analysis of spectroscopic data, and by comparison of their NMR spectral data with those of the related model compounds.


Asunto(s)
Aminas/aislamiento & purificación , Compuestos de Anilina/aislamiento & purificación , Antozoos/química , Quinonas/aislamiento & purificación , Aminas/química , Compuestos de Anilina/química , Animales , Estructura Molecular , Resonancia Magnética Nuclear Biomolecular , Quinonas/química
17.
Am J Chin Med ; 37(5): 967-75, 2009.
Artículo en Inglés | MEDLINE | ID: mdl-19885956

RESUMEN

Platycodi Radix is the root of Platycodon grandiflorum (Jacq.) A. DC and has been used as a traditional medicine in China. According to the theory of traditional Chinese medicine, Platycodi Radix (PR) possesses the character of lung meridian tropism (Guijing) and has selective effects on the lung and respiratory system. The aim of this study was to confirm the antioxidant effects of saponins from Platycodi Radix (PRS), with emphasis on its selective inhibition of lipid peroxidation in different tissues. The hydroxyl radical scavenging activity was determined by a H(2)O(2)/Fe(2+) system; a modified thiobarbituric acid reactive species assay was used to measure the lipid peroxide in rats' tissues. These antioxidant activities were compared to ascorbic acid (Vc). The results showed that PRS had antioxidant activities in various antioxidant systems. And the inhibition capability of lipid peroxidation of PRS and Vc were excellent, but differed greatly in different tissues. These results suggested that PRS had antioxidant effects and selective inhibition of lipid peroxidation. It indicated that the mechanism of Platycodi Radix to treat some diseases might be related to its antioxidant activity, especially its tissue selective effects. However, further study is needed.


Asunto(s)
Antioxidantes/farmacología , Peroxidación de Lípido/efectos de los fármacos , Raíces de Plantas/química , Platycodon/química , Saponinas/farmacología , Animales , Cromatografía Líquida de Alta Presión , Relación Dosis-Respuesta a Droga , Depuradores de Radicales Libres/farmacología , Riñón/efectos de los fármacos , Riñón/metabolismo , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Malondialdehído/metabolismo , Miocardio/metabolismo , Extractos Vegetales/análisis , Extractos Vegetales/farmacología , Ratas , Ratas Wistar , Saponinas/análisis , Bazo/efectos de los fármacos , Bazo/metabolismo , Sustancias Reactivas al Ácido Tiobarbitúrico/metabolismo
18.
Yao Xue Xue Bao ; 44(11): 1258-61, 2009 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-21351725

RESUMEN

Two erythrodiol triterpene fatty esters, 3beta-dodecanoyl erythrodiol (1) and 3beta-tetradecanoyl erythrodiol (2), were isolated from Scorzonera mongolica. Their structures were elucidated on the basis of IR, MS and extensive 2D NMR spectroscopic analysis. Compound 1 was identified to be a new compound and 2 was confirmed to be a new natural compound. Their antitumor effects in vitro were evaluated with MTT and SRB assays, but compounds 1 and 2 only showed moderate cytotoxicities on A-549 cell line.


Asunto(s)
Antineoplásicos Fitogénicos/aislamiento & purificación , Medicamentos Herbarios Chinos/aislamiento & purificación , Scorzonera/química , Triterpenos/aislamiento & purificación , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Carcinoma Hepatocelular/patología , Línea Celular Tumoral/efectos de los fármacos , Medicamentos Herbarios Chinos/química , Medicamentos Herbarios Chinos/farmacología , Humanos , Leucemia P388/patología , Neoplasias Hepáticas/patología , Neoplasias Pulmonares/patología , Espectroscopía de Resonancia Magnética , Ratones , Estructura Molecular , Plantas Medicinales/química , Triterpenos/química , Triterpenos/farmacología
19.
Yao Xue Xue Bao ; 44(11): 1228-32, 2009 Nov.
Artículo en Zh | MEDLINE | ID: mdl-21355323

RESUMEN

The purpose of this study is to determine if paeonol can protect hippocampal neurons against injury due to oxygen-glucose deprivation (OGD) injury. The rat neurons were cultured in an OGD environment and the model of OGD injury was established. Paeonol and MK-801, a positive control drug, were added before deprivation. Neuron viability was measured by the reduction of MTT; glutamate was analyzed by amino acid analyzer; binding activity of NMDA receptor was evaluated by liquid scintillation counting and the expression of NMDA receptor NR1 subunit mRNA was semiquantitatively determined by RT-PCR. Compared with OGD injury group, paeonol treatment obviously increased cell survival rate and reduced the binding activity of NMDA receptors and the release of glutamate; and down-regulating the expression of NR1 subunit. These results suggest that paeonol may exhibit its protective effect against OGD injury by the action on NMDA receptor of rats.


Asunto(s)
Acetofenonas/farmacología , Glucosa/deficiencia , Fármacos Neuroprotectores/farmacología , Paeonia , Receptores de N-Metil-D-Aspartato/metabolismo , Acetofenonas/aislamiento & purificación , Animales , Hipoxia de la Célula , Supervivencia Celular/efectos de los fármacos , Células Cultivadas , Maleato de Dizocilpina/farmacología , Ácido Glutámico/metabolismo , Hipocampo/citología , Neuronas/citología , Fármacos Neuroprotectores/aislamiento & purificación , Paeonia/química , Plantas Medicinales/química , Unión Proteica , ARN Mensajero/metabolismo , Distribución Aleatoria , Ratas , Ratas Wistar , Receptores de N-Metil-D-Aspartato/genética
20.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(11): 3138-40, 2009 Nov.
Artículo en Zh | MEDLINE | ID: mdl-20102003

RESUMEN

An inductively coupled plasma mass spectrometry (ICP-MS) for determination of the contents of 27 inorganic elements in Limonium bicolor after microwave digestion of the sample was developed. The accuracy of the method was evaluated by the analysis of corresponding inorganic elements in standard reference materials (GBW 07605), and matrix effect and signal drift were compensated by using the internal standard elements (Ge, In and Bi). By applying the proposed method, the contents of 27 inorganic elements in Limonium bicolor collected from Dongying (Shandong Province of China) were determined. The precision of measurement ranges from 1.5% to 9.7% in terms of relative standard deviation. The recoveries and the limits of detection are in the range of 92.4%-107.2% and 0.002-0.081 microg x L(-1), respectively. It is indicated that the proposed method has the advantages of simplicity, speediness and sensitivity. The results showed that the Limonium bicolor are rich in major elements Na, K, Ca and Mg and trace elements Fe, Mn, Zn, Cr and Cu. This paper provides scientific basis for deeply studying the relation between the inorganic elements and the drug effects of Limonium bicolor.


Asunto(s)
Espectrometría de Masas , Plumbaginaceae/química , Oligoelementos/análisis , Microondas
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